Waking and genioglossus muscle responses to upper airway pressure oscillation in sleeping dogs

We studied waking and genioglossus electromyographic (EMGgg) responses to oscillating pressure waves applied to the upper airways of three sleeping dogs. The dogs were previously prepared with a permanent side-hole tracheal stoma and were trained to sleep with a tight-fitting snout mask, hermetically sealed in place, while breathing through a cuffed endotracheal tube inserted through the tracheostomy. Sleep state was determined by behavioral, electroencephalographic, and electromyographic criteria, and EMGgg activity was measured using fine bipolar electrodes inserted directly into the muscle. Oscillatory pressure waves of 30 Hz and +/- 3 cmH2O (tested at atmospheric and subatmospheric upper airway pressures) were applied at the dog's nostrils or larynx, either constantly for a period of 1 min or in 0.5-s bursts. We found that the pressure stimulus had two major effects. First, it was a potentially powerful arousal-promoting stimulus. Arousal occurred in 78% of tests in slow-wave sleep (SWS) and 55% of tests in rapid-eye-movement (REM) sleep, with swallowing and sighing accompanying many of the arousals. Second, it produced an immediate and sustained augmentation of EMGgg, in wakefulness, SWS, and REM sleep. We conclude that oscillatory pressure waves in the upper airway, as found in snoring, produce reflex responses that help maintain upper airway patency during sleep. Loss of this type of reflex might contribute to the onset of obstructive sleep apnea in chronic snorers.     

Role of upper airway in ventilatory control in awake and sleeping dogs

We examined the role of the upper airway in the regulation of the pattern of breathing in six adult dogs during wakefulness and sleep. The dogs breathed through a fenestrated endotracheal tube inserted through a tracheostomy. The tube was modified to allow airflow to be directed either through the nose or through the tracheostomy. When airflow was diverted from nose to tracheostomy there was an abrupt increase in the rate of expiratory airflow, resulting in prolongation of the end-expiratory pause but no change in overall expiratory duration or respiratory frequency. Furthermore, electromyogram recordings from implanted diaphragmatic and laryngeal muscle electrodes did not show any changes that could be interpreted as an attempt to delay expiratory airflow or increase end-expiratory lung volume. The effects of switching from nose to tracheostomy breathing could be reversed by adding a resistance to the endotracheal tube so as to approximate upper airway resistance. The findings indicate that under normal conditions in the adult dog upper airway receptors play little role in regulation of respiratory pattern and that the upper airway exerts little influence on the maintenance of end-expiratory lung volume.     

Arousal responses to airway occlusion in sleeping dogs: comparison of nasal and tracheal occlusions

Previous studies have shown that the arousal threshold to hypoxia, hypercapnia, and tracheal occlusions is greatly depressed in rapid-eye-movement (REM) sleep compared with slow-wave sleep (SWS). The aim of this study was to compare the arousal thresholds in SWS and REM sleep in response to an upper airway pressure stimulus. We compared the waking responses to tracheal (T) vs. nasal (N) occlusion in four unanesthetized, naturally sleeping dogs. The dogs either breathed through a tracheal fistula or through the snout using a fiberglass mask. A total of 295 T and 160 N occlusion tests were performed in SWS and REM sleep. The mean time to arousal during N and T tests was variable in the same dog and among the dogs. The mean time to arousal in SWS-tracheal occlusion was longer than that in N tests in only two of the four dogs. The total number of tests inducing arousal within the first 15 s of SWS-nasal occlusion tests was significantly more than that of T tests (N: 47%; T: 27%). There was a marked depression of arousal within the initial 15 s of REM sleep in T tests compared with N tests (N: 21%; T: 0%). The frequency of early arousals in REM tests was less than that of SWS for both N and T tests. The early arousal in N occlusion is in sharp contrast to the well-described depressed arousal responses to hypoxia, hypercapnia, and asphyxia. This pattern of arousal suggests that the upper airway mechanoreceptors may play an important role in the induction of an early arousal from nasal occlusion.     

Superior laryngeal and hypoglossal afferents tonically influence upper airway motor excitability in anesthetized rats.

Upper airway (UA) muscle activity is stimulated by changes in UA transmural pressure and by asphyxia. These responses are reduced by muscle relaxation. We hypothesized that this is due to a change in afferent feedback in the ansa hypoglossi and/or superior laryngeal nerve (SLN). We examined 1) the glossopharyngeal motor responses to UA transmural pressure and asphyxia and 2) how these responses were changed by muscle relaxation in animals where one or both of these afferent pathways had been sectioned bilaterally. Experiments were performed in 24 anesthetized, thoracotomized, artificially ventilated rats. Baseline glossopharyngeal activity and its response to UA transmural pressure and asphyxia were moderately reduced after bilateral section of the ansa hypoglossi (P < 0.05). Conversely, bilateral SLN section increased baseline glossopharyngeal activity, augmented the response to asphyxia, and abolished the response to UA transmural pressure. Muscle relaxation reduced resting glossopharyngeal activity and the response to asphyxia (P < 0.001). This occurred whether or not the ansa hypoglossi, the SLN, or both afferent pathways had been interrupted. We conclude that ansa hypoglossi afferents tonically excite and SLN afferents tonically inhibit UA motor activity. Muscle relaxation depressed UA motor activity after section of the ansa hypoglossi and SLN. This suggests that some or all of the response to muscle relaxation is mediated by alterations in the activity of afferent fibers other than those in the ansa hypoglossi or SLN.     

Ventilatory responses to specific CNS hypoxia in sleeping dogs.

Our study was concerned with the effect of brain hypoxia on cardiorespiratory control in the sleeping dog. Eleven unanesthetized dogs were studied; seven were prepared for vascular isolation and extracorporeal perfusion of the carotid body to assess the effects of systemic [and, therefore, central nervous system (CNS)] hypoxia (arterial PO(2) = 52, 45, and 38 Torr) in the presence of a normocapnic, normoxic, and normohydric carotid body during non-rapid eye movement sleep. A lack of ventilatory response to systemic boluses of sodium cyanide during carotid body perfusion demonstrated isolation of the perfused carotid body and lack of other significant peripheral chemosensitivity. Four additional dogs were carotid body denervated and exposed to whole body hypoxia for comparison. In the sleeping dog with an intact and perfused carotid body exposed to specific CNS hypoxia, we found the following. 1) CNS hypoxia for 5-25 min resulted in modest but significant hyperventilation and hypocapnia (minute ventilation increased 29 +/- 7% at arterial PO(2) = 38 Torr); carotid body-denervated dogs showed no ventilatory response to hypoxia. 2) The hyperventilation was caused by increased breathing frequency. 3) The hyperventilatory response developed rapidly (<30 s). 4) Most dogs maintained hyperventilation for up to 25 min of hypoxic exposure. 5) There were no significant changes in blood pressure or heart rate. We conclude that specific CNS hypoxia, in the presence of an intact carotid body maintained normoxic and normocapnic, does not depress and usually stimulates breathing during non-rapid eye movement sleep. The rapidity of the response suggests a chemoreflex meditated by hypoxia-sensitive respiratory-related neurons in the CNS.     

Influence of upper airway negative pressure reflex on response to airway occlusion in sleeping infants

Artificially produced upper airway suction inhibits the diaphragm in animals and infants; however, the effects of spontaneously generated suction in humans are unknown. We studied nine tracheostomized infants because separation of the upper from the lower airway allowed us to channel suction created by an occluded inspiratory effort to both upper and lower airways (upper + lower airway occlusions) or to the lower airway only (lower airway occlusion). The tracheostomy airway was briefly occluded at end expiration during quiet sleep. In upper + lower airway occlusions, peak airway pressure of the first occluded breath was less negative and rate of pressure decrease slower than that of lower airway occlusions, indicating that upper airway suction inhibits thoracic inspiratory muscles. The threshold for this response was less than or equal to 4 cmH2O suction pressure. The effect on inspiratory time was variable. A decrease in slope of the inspiratory pressure waveform occurring at approximately 0.12 s after inspiration onset was more marked in upper + lower airway occlusions. We conclude that infants have an upper airway reflex response to inspiratory pressure that alters not only the peak and slope but also the shape of the inspiratory pressure waveform.     

Ragweed sensitization alters pulmonary vascular responses to bronchoprovocation in beagle dogs

Theodorou, Andreas, Natalie Weger, Kathleen Kunke, KyooRhee, David Bice, Bruce Muggenberg, and Richard Lemen. Ragweed sensitization alters pulmonary vascular responses to bronchoprovocation in beagle dogs. J. Appl. Physiol.83(3): 912-917, 1997.In ragweed (RW)-sensitized beagle dogs, wetested the hypothesis that reactivity of the pulmonary vasculature wasenhanced with aerosolized histamine (Hist) and RW. Seven dogs wereneonatally sensitized with repeated intraperitoneal RW injections, and12 dogs were controls (Con). The dogs were anesthetizedwith intravenous chloralose, mechanically ventilated, and instrumentedwith femoral arterial and pulmonary artery catheters. Specific lungcompliance(CL_sp),specific lung conductance (G_sp),systemic vascular resistance index, and pulmonary vascular resistanceindex (PVRI) were measured before and after bronchoprovocation withHist and RW. After Hist inhalation (5 breaths of 30 mg/ml), both Conand RW dogs had significant (P < 0.05) decreases inCL_sp(51 ± 4 and 53 ± 5%, respectively) andG_sp (65 ± 5 and69 ± 3%, respectively), but only RW-sensitized dogs had asignificant increase in PVRI (38 ± 10%). After RW inhalation (60 breaths of 0.8 mg/ml), only RW-sensitized dogs had significant increases (62 ± 20%) in PVRI and decreases inG_sp (77 ± 4%) and CL_sp(65 ± 7%). We conclude that, compared with Con,RW-sensitized beagle dogs have increased pulmonary vasoconstrictiveresponses with Hist or RW inhalation.

     

An isolated upper airway preparation in conscious dogs

The purpose of this study was to develop an isolated upper airway preparation in conscious dogs. Each of the four dogs was trained to wear an individually fitted respiratory mask and surgically prepared with two side-hole tracheostomies. After full recovery, one endotracheal tube was inserted caudally into the lower tracheostomy hole and another tube cranially into the upper tracheostomy. When the two endotracheal tubes were connected to a breathing circuit including a box-balloon system, the magnitude and pattern of the inspiratory flow through the upper airway were identical to that inhaled spontaneously into the lungs by the dogs, but the gas medium inhaled into the upper airway could be independently controlled. Thus it allowed test gas mixtures to be inhaled spontaneously through an isolated upper airway. One limitation was that the inspired gas remained in the upper airway during expiration, but this can be corrected by a simple modification of the breathing circuit. This preparation was tested in studying the respiratory effects of upper airway exposure to CO2 gas mixtures. Our results showed small but significant reduction in both rate and volume of respiration when the concentration of CO2 gas mixture inhaled through the upper airway exceeded 5%. Irregular breathing patterns were frequently elicited in these dogs by higher concentrations (greater than 12%) of CO2.     

Soft palate muscle responses to negative upper airway pressure

The afferentpathways and upper airway receptor locations involved in negative upperairway pressure (NUAP) augmentation of soft palate muscle activity havenot been defined. We studied the electromyographic (EMG) response toNUAP for the palatinus, tensor veli palatini, and levator veli palatinimuscles in 11 adult, supine, tracheostomized, anesthetized dogs. NUAPwas applied to the nasal or laryngeal end of the isolated upper airwayin six dogs and to four to six serial upper airway sites from the nasalcavity to the subglottis in five dogs. When NUAP was applied at thelarynx, peak inspiratory EMG activity for the palatinus and tensorincreased significantly (P < 0.05) and plateaued at a NUAP of 10cmH₂O. Laryngeal NUAP failed toincrease levator activity consistently. Nasal NUAP did not increase EMGactivity for any muscle. Consistent NUAP reflex recruitment of softpalate muscle activity only occurred when the larynx was exposed to the stimulus and, furthermore, was abolished by bilateral section of theinternal branches of the superior laryngeal nerves. We conclude thatsoft palate muscle activity may be selectively modulated by afferentactivity originating in the laryngeal and hypopharyngeal airway.     

Induction of upper airway occlusion in sleeping individuals with subatmospheric nasal pressure

In collapsible biologic conduits, occlusion and cessation of flow occur when upstream pressure falls below a critical pressure (Pcrit). To examine the relationship between Pcrit and the development of upper airway occlusion, we examined the relationship between maximal inspiratory airflow and nasal pressure in seven normal subjects during sleep. At varying levels of subatmospheric pressure applied to a nasal mask during non-rapid-eye-movement (NREM) sleep, maximal inspiratory airflow decreased in proportion to the level of nasal pressure. When nasal pressure fell below a Pcrit, subjects demonstrated upper airway occlusions terminated by arousals. In these normal subjects, the upper airway Pcrit was found to be -13.3 +/- 3.2 (SD) cmH2O. In four subjects who sustained sleep while nasal pressure remained below the Pcrit, recurrent occlusive apneas were demonstrated. The relationship between maximal inspiratory airflow and nasal pressure in each subject was fit by linear regression and demonstrated upper airway Pcrit at the zero-flow intercept that were not significantly different from those observed experimentally. These data demonstrate that the normal human upper airway during sleep is characterized by a negative Pcrit and that occlusion may be induced when nasal pressure is decreased below this Pcrit.